Structural studies on biological macromolecules and macromolecular assemblies have been performed by high resolution electron microscopy complemented by optical diffraction and digital image processing in a new facility designed for this purpose and still under development. Micrographs of human immunoglobulin IgG crystals have been analyzed extensively to determine the fidelity of electron images and to characterize the specificity of stain distribution. Compared to a reference structure derived from X-ray diffraction, the computer-optimized micrographs show excellent fidelity to 2 nm resolution. Furthermore, the distribution of uranyl stain is predominantly nonspecific. The complete helical structure of beet necrotic yellow vein virus, a rodlike plant virus possessing a quadripartite genome of RNA has been solved by these methods. Initial progress has also been made towards solving the molecular packing within keratin filaments, the structures of tetragonal particle patches observed in membrane preparations of human erythrocytes membrane, and the molecular architecture of the bacteriophage T7 capsid.